This project extends our earlier studies of the rapid fatty acid (FA) esterification-hydrolysis cycle that we have described in Ehrlich ascites carcinoma and explores other aspects of tumor-host lipid transport and metabolism that have not been adequately studied because of their highly complex and difficult nature. First, we shall try to establish whether the FA esterificationhydrolysis cycle is more rapid in malignant than in nonmalignant tumors or normal tissues. By studying this cycle both in vivo and in vitro we may be able to suggest new strategies relevant to diagnosis and treatment of cancer. We also wish to test current hypotheses regarding the effect of cancer growth on host lipid metabolism. We will continue to explore the possible existence of unique or altered mechanisms of lipid transport to the carcinoma. In particular, we shall extend our earlier hypothesis that cancer cells can induce rapid lipolysis in adjacent adipose tissue and the direct delivery of free fatty acids to the carcinoma. We also shall see whether alteration of fatty acids in cancer cell membrane lipids increases the cells' susceptibility to chemo-\and immunotherapy and whether well-defined changes in cancer cell membranes alter the tumor-induced metabolic aberrations in the host. Finally, we shall study whether and how controlled alteration of the membrane fatty acid composition in culture or in vivo (peritoneal isolation) will alter pathways and rates of lipid and carbohydrate metabolism in cancers. In the course of testing these several hypotheses, we shall continue our efforts to develop radioactive tracer techniques and multicompartmental approaches for studying complex metabolic interactions between tumor and host tissues in vivo.